Classifications

• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
  • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
  • G01N35/02—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a plurality of sample containers moved by a conveyor system past one or more treatment or analysis stations
  • G01N35/025—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a plurality of sample containers moved by a conveyor system past one or more treatment or analysis stations having a carousel or turntable for reaction cells or cuvettes
• • C—CHEMISTRY; METALLURGY
  • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
  • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
  • C12M23/00—Constructional details, e.g. recesses, hinges
  • C12M23/48—Holding appliances; Racks; Supports
• • C—CHEMISTRY; METALLURGY
  • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
  • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
  • C12M23/00—Constructional details, e.g. recesses, hinges
  • C12M23/44—Multiple separable units; Modules
• • C—CHEMISTRY; METALLURGY
  • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
  • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
  • C12M23/00—Constructional details, e.g. recesses, hinges
  • C12M23/50—Means for positioning or orientating the apparatus
• • C—CHEMISTRY; METALLURGY
  • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
  • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
  • C12M41/00—Means for regulation, monitoring, measurement or control, e.g. flow regulation
  • C12M41/48—Automatic or computerized control
• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
  • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
  • G01N35/02—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a plurality of sample containers moved by a conveyor system past one or more treatment or analysis stations
  • G01N35/04—Details of the conveyor system
  • G01N2035/0439—Rotary sample carriers, i.e. carousels
  • G01N2035/0441—Rotary sample carriers, i.e. carousels for samples
• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
  • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
  • G01N35/02—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a plurality of sample containers moved by a conveyor system past one or more treatment or analysis stations
  • G01N35/04—Details of the conveyor system
  • G01N2035/0474—Details of actuating means for conveyors or pipettes
  • G01N2035/0482—Transmission
  • G01N2035/0484—Belt or chain
• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
  • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
  • G01N35/02—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor using a plurality of sample containers moved by a conveyor system past one or more treatment or analysis stations
  • G01N35/04—Details of the conveyor system
  • G01N2035/0474—Details of actuating means for conveyors or pipettes
  • G01N2035/0491—Position sensing, encoding; closed-loop control
  • G01N2035/0494—Detecting or compensating piositioning errors

Definitions

• This invention relates to an upright carousel that provides translational movement of multiple biologic production units along a defined vertical path while maintaining each individual unit stable relative to gravity and further provides for separate dynamic axial rotation of each independent unit.
• the carousel is automated and adaptable for use with a variety of modular biologic production units designed for cell culture and/or tissue culture systems in various clinical and laboratory settings.
• the carousel and related systems and methods allow ergonomic and practical access to each of the biologic production units.
• an upright automated carousel configured to support several biological production units that can be translationally moved along the vertical path of the carousel in unison and stopped to a user selected position for access to any one of the biological production units.
• each individual unit remains stable relative to gravity, that is, remains properly orientated horizontal to gravity.
• the automated carousel further provides for individual dynamic adjustment of axial rotation of any one or all of the units. Proper orientation of each of the units relative to gravity is maintained during active translation of the units and when the carousel is stationary.
• the individual dynamic adjustment of the axial orientation of any one or all of the units can be actuated during active translational movement of the units or when the carousel is stationary
• the operation of the automated carousel for user positioning does not negatively affect the cell and/or tissue culture/engineering processes that are supported within any one of the biological production units.
• the automated carousel is configured so that each of the biological production units supported on the carousel is independently operable and customized with respect to the cell and/or tissue culture/engineering processes that are supported within any one of the biological production units.
• the biological production units supported on the carousel are so linked that the operational resources required for each of the biological production units are optionally one central means for ease of use.
• the linkage to the central operational resources is operationally maintained during translational movement of the biological units along the vertical curved path of the carousel and during any individual adjustment of axial rotation of any one of the units.
• the automated carousel of the invention is advantageously configured to utilize vertical space for the distribution, operation and uniform translational movement of multiple biological production units arranged in a close spatial relationship along its curved vertical path.
• Translational movement is in a vertical plane and follows the curved shape of the carousel.
• Translational movement may be up to about 180 degrees clockwise or counterclockwise, of varying speeds and is user controlled.
• the translational movement is designed to be precise and in controlled increments such that an operator (no matter what height) can position any one of the biological units to a position for ergonomic access whether in a standing or a sitting position.
• the carousel is configured with a safety stop mechanism to stop movement at any time as desired or required.
• the axial rotation of any one individual biological production unit may also be clockwise or counterclockwise to provide a rocking motion or for agitation.
• Attachment of the biological production units to the carousel is reversible such that each unit can be inspected, removed, replaced or repositioned to a different position on the carousel or to a different carousel.
• the biological production units are attached in a cantilevered orientation to allow easier access by a user and to maintain the efficient use of floor space.
• each of the biological production units mounted on the carousel may support a different cell culture and/or tissue culture system therein customized for a specific need or a specific patient.
• the automated carousel may be provided as a system disposed vertically within a vertical housing for central operation and central provision of operational resources to each of the independently controlled biological production units that function to support a cell and/or tissue culture system therein.
• the vertical housing serves as a support frame and attachment structure for the carousel to maintain an upright positioning of the carousel and for its operation.
• the vertical housing is configured to readily permit reversible attachment of the biological production units, their proper translational movement along the carousel shape, and for user access.
• the vertical housing has a supporting base and retractable wheels for ease of relocation.
• the vertical housing is configured for ease of assembly and disassembly, for centrally storing required resources and for user safety.
• the carousel of the invention can provide increased expandability, by taking full advantage of the height of a biological production facility.
• Several carousels can be arranged and used in series. Therefore numerous biological production units can be run in a production facility in a space efficient yet operator accessible manner.
• the carousel is used in conjunction with one or more controllers, controller
• the carousel for translating a plurality of biological units in unison along a vertical elliptical orbit while maintaining each individual biological load stable relative to gravity, and providing for individual dynamic axial rotation of any one or all of the biological units.
• the carousel comprises a spacing adjustment means to adjust the spacing of each biological unit relative to adjacent biological units so as to maximize the spatial density of biological units in selected zones of the carousel by close spacing and enhance user access to biological units in other selected zones by open spacing.
• each of the biological units are independently operable and linked to a central source of operational resources.
• the biological loads are sensitive to orientation relative to gravity.
• the carousel comprises an upright drive track and a support track vertically offset from one another and held together by a plurality of linkage mechanisms, each of the linkage mechanisms adapted to support a biological unit during translational movement along the elliptical orbit of the drive track and support track.
• the biological units are supported in a cantilevered position for ease of user access once positioned.
• the plurality of cantilevered biological units are translationally positioned in unison along an upright frame comprising two vertically offset tracks.
• the tracks are substantially oval. In aspects oval closed loops.
• the speed and direction of translation (clockwise or counter-clockwise) is user controlled and adjustable.
• alignment of each cantilevered biological unit is substantially maintained relative to gravity during translational movement of the units or when the carousel is stationary.
• the carousel provides dynamic adjustment of axial orientation (bi-directional) relative to gravity of each independent cantilevered biological unit during translational movement of the units or when stationary.
• precise positioning of each cantilevered biological unit is user controlled for ergonomic access.
• the cantilevered biological unit is a cantilevered biological production unit.
• the cantilevered biological production unit operationally supports an automated cell culture and/or tissue engineering system.
• each of the biological production units are independently operable to provide a customized cell culture and/or tissue engineering systems.
• the cell culture and/or tissue engineering systems are for autologous cell therapies.
• the carousel reduces overall space/storage footprints while increasing employee safety and efficiency.
• the carousel is part of a system that further comprises a housing for vertical operational support of the carousel and means for connection of each biological production unit in succession to a central source of auxiliaries and resources.
• an automated carousel system for organizing, storing, and ergonomically accessing cell and/or tissue engineering systems enclosed in a biological production unit.
• the automated carousel and systems incorporating the carousel greatly increases facility biological operational capacity by fully utilizing overhead space to recover up to 70% of the floor space required by conventional biological culturing systems.
• an automated vertical track assembly for supporting a plurality of biological units, wherein the carousel is configured for:
• each of the biological units is independently operable support a customized automated cell and tissue culture system therein;
• each of said biological units is interlinked to share a central source of operational resources.
• a vertical carousel comprising a plurality of biological units substantially geometrically constrained to translationally move in unison in a vertical elliptical orbit while maintaining the proper orientation of each of the plurality of biological units with respect to gravity, and separately axially rotating any independent one or more of the plurality of biological units.
• a vertical carousel comprising:
• - a plurality of biological units substantially geometrically constrained for translational movement along a vertical elliptical orbit in unison while maintaining a stable orientation of each of the plurality of biological units with respect to gravity, and for separate axial rotation of any one or more of the plurality of biological units; - means to control the translational movement of the biological units for user positioning;
• an automated carousel comprising:
• a vertical track assembly comprising a drive track and a support track vertically offset from one another;
• each translation assembly supporting a cantilevered biological unit
• said plurality of translation assemblies is configured for providing (i) translational movement along the connected tracks in unison while maintaining the proper orientation of each cantilevered biological unit with respect to gravity, and separately, (ii) axial rotation of each biological unit.
• a system for maximizing cell and/or tissue engineering production comprising a plurality of automated carousels as described herein supported and arranged in series.
• a further aspect of the invention is a method for maximizing cell and/or tissue engineering production, the method comprising providing a series of the automated carousel system as described herein in a production facility.
• a translation assembly for a vertical carousel having a drive track and vertically off set support track, for supporting a biological unit for translational movement and independent axial rotation
• the translation assembly comprising: a first end defining a reversible coupling for receiving an input shaft of a biological unit; a central hub comprising:
• an inner hub comprising a separate mechanism configured for the axial rotation of the biological unit
• a second end having a vertically downward extending resistance arm mounted via the inner hub and at its vertically lowest point a pivotally connected support carriage cooperatively engaged with the support track for translational movement thereon, wherein the vertically extending resistance arm prevents rotation of the inner hub and is maintained in a vertical orientation by geometrical constraint arising from the fixed vertical offset of the drive track and support track during translational movement along the tracks.
• an automated carousel system for the distribution and ergonomic positioning of multiple biological production units each of the units comprising an automated individually operable cell and/or tissue culture system, the automated carousel system comprising:
• an automated carousel comprising:
• a vertical track assembly comprising a drive track and a support track vertically offset therefrom;
• each of said plurality of translation assemblies supporting a cantilevered biological production unit, wherein said plurality of translation assemblies is configured for providing (i) translational movement along the connected tracks in unison while maintaining the proper orientation of each cantilevered biological production unit with respect to gravity, and separately, (ii) axial rotation of each biological production unit;
• an automated carousel system that comprises a plurality of independent culture systems each supported within a biological production unit, the method comprising:
• a vertical track assembly comprising a drive track and a support track vertically offset therefrom;
• each of said plurality of translation assemblies supporting a cantilevered biological production unit, wherein said plurality of translation assemblies is configured for providing (i) translational movement along the connected tracks in unison while maintaining the proper orientation of each cantilevered biological production unit with respect to gravity, and separately, (ii) axial rotation of each biological production unit;
• a method for increasing biological production capacity utilizing cell and/or tissue culture systems in a production facility comprising:
• each housing a cell and/or tissue culture system on an upright automated carousel comprising a plurality of translation assemblies connecting a drive track and a support track at spaced apart positions, each of said plurality of translation assemblies supporting a cantilevered biological production unit, wherein said plurality of translation assemblies is configured for providing (i) translational movement along the connected tracks in unison while maintaining the proper orientation of each cantilevered biological production unit with respect to gravity, and separately, (ii) axial rotation of each biological production unit.
• an ergonomic automated carousel for supporting automated individually operable biological systems comprising:
• each of said plurality of translation assemblies supporting a cantilevered biological production unit, wherein said plurality of translation assemblies is configured for providing (i) translational movement along the connected tracks in unison while maintaining the proper orientation of each cantilevered biological production unit with respect to gravity, and separately, (ii) axial rotation of each biological production unit;
• a further aspect of the invention is a method for ergonomically positioning an automated selected cell culture and/or tissue engineering system for inspection by a user, the method comprising: sending one or more translational movement operating instructions to an upright carousel comprising a plurality of spaced apart cantilevered biological production units configured to contain the cell and/or tissue culture system for translationally moving the plurality of cantilevered biological production units in unison via a remote management device, the one or more translational movement instructions comprising information about the location on the carousel of a target biological production unit for positioning and information regarding physical measurement specifications of a specific user standing or seated,
• the carousel comprising a controller and a communication interface, the controller being configured to:
• the automated upright carousel can operationally support any desired number of biological production units such as at least two biological production units, up to about six units, up to about eight units, up to about 10 units, up to about 12 units, up to about 14 units, up to about 16 units, up to about 18 units or up to about 20 units or more.
• the automated carousel enables ergonomic access to a specific independent cell and/or tissue culture system without disturbance of the biological processes underway in any of the other independent multiple cell and/or tissue culture systems.
• the carousel is generally height adjustable and easily configurable to a wide variety of user sizes, shapes and weights.
• the ergonomic carousel is configured to alleviate existing muscular, skeletal or nervous system issues and/or configured to prevent such issues in the first instance for laboratory personnel.
• the ergonomic carousel is suitable for vertical adjustment for a sitting
• An automated vertical track assembly for supporting a plurality of biological units, wherein the vertical track assembly is configured for:
• each of the biological units is independently operable to support a customized automated cell and tissue culture system therein;
• each of said biological units is interlinked to share a central source of operational resources.
• a vertical carousel comprising a plurality of biological units substantially geometrically constrained to translationally move in unison in a predefined orbit while maintaining the proper orientation of each of the plurality of biological units with respect to gravity, and separately axially rotating any independent one or more of the plurality of biological units.
• a vertical carousel comprising a plurality of biological units substantially geometrically constrained to translationally move in unison in a predefined orbit while maintaining the proper orientation of each of the plurality of biological units with respect to gravity, and separately the ability to adjust the spacing of each biological unit relative to adjacent biological units so as to maximize the spatial density of biological units in selected zones of the carousel by close spacing and enhance user access to biological units in other selected zones by open spacing.
• a vertical carousel comprising:
• An automated carousel comprising:
• a vertical track assembly comprising a drive track and a support track vertically offset from one another;
• each translation assembly supporting a cantilevered biological unit
• said plurality of translation assemblies is configured for providing (i)
• each of the plurality of translation assemblies is a horizontal hub assembly.
• said horizontal hub assembly comprises: a first end defining a reversible coupling for receiving an input shaft of the cantilevered biological unit;
• a central hub comprising:
• an inner hub comprising a separate mechanism configured for the axial rotation of the biological unit; and a second end having a vertically downward extending resistance arm mounted via the inner hub and at its vertically lowest point a pivotally connected support carriage cooperatively engaged with the support track for translational movement thereon, wherein the vertically extending resistance arm prevents rotation of the inner hub and is maintained in a vertical orientation by geometrical constraint arising from the fixed vertical offset of the drive track and support track during translational movement along the tracks.
• connection means comprises cabling enclosing separate resources, the cabling originating from a central source and connecting each successive biological unit on said carousel.
• the automated carousel of claim 12 further operatively connected to a means for interrupting and/or stopping translational movement.
• said cell and/or tissue engineering system performs one or more of: sterile reception/storage of tissue biopsy; automated monitoring of digestion process; digestion of biopsy tissue to yield disassociated cells;
• An automated system for maximizing cell and/or tissue engineering production comprising an automated carousel of any one of claims 1 to 19 supported within a vertical housing and operationally connected to one or more controllers for control of translation movement by a user and precise ergonomic positioning of the biological unit for inspection thereof.
• an automated carousel comprising:
• a vertical track assembly comprising a drive track and a support track vertically offset therefrom;
• each of said plurality of translation assemblies supporting a cantilevered biological production unit
• said plurality of translation assemblies is configured for providing (i) translational movement along the connected tracks in unison while maintaining the proper orientation of each cantilevered biological production unit with respect to gravity, and separately, (ii) axial rotation of each biological production unit; - means for independent biological control of each cell and/or tissue culture system within each of said biological production units;
• each biological production unit comprises a connected interface for communication by a user, said connected interface connected to the computer.
• a method for maximizing cell and/or tissue engineering production comprising providing one or more automated carousels system of any one of claims 1 to 19 in a production facility.
• a method for improving ergonomics for users of an automated carousel system that comprises a plurality of independent culture systems each supported within a biological production unit, the method comprising:
• a vertical track assembly comprising a drive track and a support track vertically offset therefrom;
• each of said plurality of translation assemblies supporting a cantilevered biological production unit, wherein said plurality of translation assemblies is configured for providing (i) translational movement along the connected tracks in unison while maintaining the proper orientation of each cantilevered biological production unit with respect to gravity, and separately, (ii) axial rotation of each biological production unit;
• each housing a cell and/or tissue culture system on an upright automated carousel comprising a plurality of translation assemblies connecting a drive track and a support track at spaced apart positions, each of said plurality of translation assemblies supporting a cantilevered biological production unit, wherein said plurality of translation assemblies is configured for providing (i) translational movement along the connected tracks in unison while maintaining the proper orientation of each cantilevered biological production unit with respect to gravity, and separately, (ii) axial rotation of each biological production unit.
• An ergonomic automated carousel for supporting automated individually operable biological systems comprising:
• each of said plurality of translation assemblies supporting a cantilevered biological production unit, wherein said plurality of translation assemblies is configured for providing (i) translational movement along the connected tracks in unison while maintaining the proper orientation of each cantilevered biological production unit with respect to gravity, and separately, (ii) axial rotation of each biological production unit;
• a method for ergonomically positioning an automated selected cell culture and/or tissue engineering system for inspection by a user comprising:
• the one or more translational movement instructions comprising information about the location on the carousel of a target biological production unit for positioning and information regarding physical measurement specifications of a specific user standing or seated, the carousel comprising a controller and a communication interface, the controller being configured to:
• Figure 1 shows one non-limiting configuration of a carousel system that comprises a carousel of the invention supported on a vertical housing having a support base and supporting a number of vertically positioned biological production units.
• One of the biological production units is in an open configuration;
• Figure 2 is a side elevational view of the carousel system of Figure 1, the arrows indicating that the carousel has about +/-180 0 vertical translational movement;
• Figure 3 is a side elevational view of the carousel system of Figure 1, the arrows showing the individual axial rotation of each independent biological production unit;
• Figure 4 shows the isolated carousel track structure supporting one representative biological production unit for simplicity
• Figure 5 shows a close up view of the isolated carousel track structure and mechanical linkage with the biological production unit
• Figure 6 shows the mechanical linkage structure of the carousel in isolation and with a central portion cut-away to show internal driving structures
• Figure 7 shows front right side isometric perspective view of a carousel with a fully populated track assembly
• Figure 8 is a front right side elevational view of the carousel system supported on a vertical housing having a support base;
• Figure 9 shows a close up of the cabling used and connected with each of the biological production units that provides required resources from a central source
• Figure 10 shows three different sizes of the carousel that are shown to support, six, eight or ten biological production units.
• Figure 11 shows representative measurements which can be used to define the range of placement of any specific biological production unit for ergonomic access by an operator.
• invention or “present invention” are non-limiting terms and not intended to refer to any single aspect of the particular invention but encompass all possible aspects as described in the specification and the claims.
• the term “about” refers to variation in the numerical quantity. In one aspect, the term “about” means within 10% of the reported numerical value. In another aspect, the term“about” means within 5% of the reported numerical value. Yet, in another aspect, the term“about” means within 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1% of the reported numerical value.
• the terms‘close’,‘approximate’ and‘practically’ denote a respective relation or measure or amount or quantity or degree that has no adverse consequence or effect relative to the referenced term or embodiment or operation or the scope of the invention.
• any terms referring to geometrical relationships such as‘vertical’, ‘horizontal’,‘parallel’,‘opposite’,‘straight’,“lateral”,“parallel”,“perpendicular” and other angular relationships denote also approximate yet functional and/or practical, respective relationships.
• substantially vertical or“substantially upright” is used to refer to an orientation where the track assemblies and support tracks described herein are suitably perpendicular (i.e., form a 90° angle relative to) to the ground or a floor of a warehouse, building, or production facility, but also includes embodiments where the tracks are within about 0°-60° from perpendicular. That is in embodiments, substantially vertical allows for the tracks to be tilted from perpendicular at an angle of about 5°, 10°, about 20°, about 30°, about 45°, etc.
• translational movement refers to the movement of an object from one place to another without a change in its orientation relative to a fixed point, as opposed to rotation, in which the object is turning about an axis.
• the carousel provides translational movement of multiple biologic production units along a substantially vertical curved path of the carousel while maintaining each individual unit fixed (i.e. horizontal, stable) with respect to its orientation to gravity.
• Translational movement can be bi-directional.
• “translates” or“translational” refers to the movement of a load supported on the carousel structure of the invention where the carousel comprises two tracks of the same size and shape that are oval, elliptical, spherical, orbital, capsule-shaped and the like. “Translate along the tracks” can be interchanged with“translation along the tracks” both meaning the movement from one position to a second position along the oval path of the upright carousel, wherein the translation does not invoke rotational inversion (of a supported unit and contents therein) during movement/travel along such frame.
• “rotation” or‘axial rotation” refers to movement of an object turning about its central axis. With respect to individual dynamic adjustment of axial rotation of a biological production unit, this means that the biological production unit rotates about its axis. This can be bi-directional. This can also be referred to as“rocking motion” or“tilt”. As used herein, a“user” is interchangeable with an“operator”.
• the term‘substantially’ denote with respect to the context a measure or extent or amount or degree that encompass a large part or most of a referenced entity, or an extent at least moderately or much greater or larger or more effective or more important relative to a referenced entity or with respect to the referenced subject matter.
• the term‘may’ denotes an option or an effect which is either or not included and/or used and/or implemented and/or occurs, yet the option constitutes at least a part of some embodiments of the invention or consequence thereof, without limiting the scope of the invention.
• “or” should be understood to have the same meaning as“and/or” as defined above.
• “or” or“and/or” shall be interpreted as being inclusive, e.g., the inclusion of at least one, but also including more than one, of a number or list of elements, and, optionally, additional unlisted items.
• the term“or” as used herein shall only be interpreted as indicating exclusive alternatives (e.g.“one or the other but not both”) when preceded by terms of exclusivity, such as “either,”“one of,”“only one of,” or“exactly one of.”
• the phrase“at least one,” in reference to a list of one or more elements, should be understood to mean at least one element selected from any one or more of the elements in the list of elements, but not necessarily including at least one of each and every element specifically listed within the list of elements and not excluding any combinations of elements in the list of elements.
• This definition also allows that elements may optionally be present other than the elements specifically identified within the list of elements to which the phrase“at least one” refers, whether related or unrelated to those elements specifically identified.
• unit is a biological unit or biological production unit. Unit is meant to generically define a biological structure used for supporting cell and tissue culture systems therein.
• cantilevered unit or“cantilevered biological production unit” are interchangeable as they refer to the same part.
• biological production unit comprises an independently operable automated cell culture and/or tissue engineering platform/ system comprising components for multifunctional operation of one or more of cell culture, cell seeding, cell digestion, cell growth, cell differentiation, cell expansion, tissue culture and tissue growth.
• the biological production unit may house and support an automated, portable, operationally multifunctional cell culture and/or tissue engineering system that
• proliferation substrate or scaffold proliferation of cells to expand cell populations cell washing and cell collection; cell seeding on or within a tissue engineering scaffold or matrix; cell differentiation to allow specialization of cellular activity; tissue formation; mechanical and/or biochemical stimulation to promote tissue maturity; harvesting the tissue engineered constructs/implants for reconstructive surgery; and storage and transportation of implantable tissue.
• this may be a tissue engineering cassette comprising one or more interlinked bioreactors that provide precise control at each stage.
• the present system selectively combines key processes to meet the unique challenges of different autologous and allogeneic clinical applications of cell and tissue therapy.
• Embedded sensors provide real time biofeedback and enable automatic adjustment in bioprocessing to accommodate natural variations in cell source behaviour.
• the entire bioprocess is contained within a disposable cassette to ensure maximum patient and operator safety and to streamline logistics. Suitable non limiting biological production units are described in U.S. 8,492,140; U.S. 9,701,932; U.S.
• automated cell culture system is an automated system that comprises several operatively linked biological production units and processors.
• bioreactors that can be controlled under automated sequences.
• bioreactors may be configured within a disposable, pre-sterilized cartridge or cassette for handling robustness and operator simplicity.
• cassette and the related control instrumentation required for implementation of the automated sequences may be contained in an environmentally controlled enclosure (a biological production unit) to achieve the following (non-limiting) operational conditions:
• the carousel is an upright carousel comprising a substantially vertical track assembly that supports and provides translational movement of a plurality of biological production units in unison or separately along the curved vertical track assembly for precise user positioning.
• the carousel suitably translates the supported biological production units simultaneously (i.e. in unison) along the curved vertical track assembly about ⁇ 180° vertical, in a clockwise or counter-clockwise direction, while maintaining a precise alignment/orientation of each of the biological production units relative to gravity.
• the carousel also comprises a means for individually dynamically adjusting the axial rotation of any of the biological production units. Surprisingly, the translational and/or axial movement of individual biological production units supporting independently operable biological systems therein, does not compromise the interconnection of the units to a central source of operational resources.
• the carousel can also translate the supported biological production units separately.
• a single unit can move, while the remaining units remain stationary (or substantially stationary), for example along a top or back of a carousel in a“bunched-up” or“collected” orientation.
• the next unit in line in the track can be separately translated out from the remaining units, allowing for work or inspection to be conducted on that unit.
• the carousel is configured within a housing powered by connection with a power source and operatively connectable with a computer for operational control (e.g. remote device, via touchpad screen, via hand held device).
• a computer for operational control (e.g. remote device, via touchpad screen, via hand held device).
• the carousel of the invention can be incorporated for use with a variety of automated cell and tissue culture systems.
• Figure 1 illustrates one non-limiting embodiment of the invention showing a
• the carousel system 1 comprises an upright carousel 10 that is supported within a framework of a vertical housing assembly 12 that serves as the support frame and attachment structure for the carousel 10.
• the vertical housing assembly 12 is mounted on a base 14.
• the vertical housing assembly 12 provides for multiple functions including mechanical support and central delivery of auxiliaries and resources (e.g. power, gases, data, etc.) and workflow management.
• auxiliaries and resources e.g. power, gases, data, etc.
• the carousel system 1 is illustrated as a“stand alone” structure requiring no additional support, and can be dimensioned to various sizes, as well as the corresponding size of the carousel, as is desired limited only by the vertical space of the particular industrial biological setting.
• the carousel system 1 shows the scale up of biological production units supporting eight biological production units 16 on its common framework.
• the carousel 10 of the carousel system is shown to be substantially vertically configured to support eight individual and operationally independent biological production units 16 in an oval arrangement that follows the curved shape of the vertical carousel track frame (not shown) in a spatially close manner.
• One of the biological production units 16 is shown in an open configuration.
• the biological production units 16 are mounted to the carousel in a configuration for easy user access. In Figure 1 this is shown to be in a cantilevered position allowing space for easy user access to the cell and tissue culture systems therein when the unit is opened.
• the biological production units 16 are translationally moved in unison or separately along the carousel track frame while maintaining their substantially even spacing and proper orientation with respect to gravity.
• GMP Good Manufacturing Practice
• the automated carousel system not only takes advantage of the unused vertical space in a biological facility but is also structured to be compact by centrally housing operational resources within the housing assembly 12. This allows specific operational resource connections linking each of the biological production units in succession to be neatly stored and merge in a manifold style cabling system to a central source of operational resources (see Figure 9). This configuration allows for the provision of resources to each biological production unit when the carousel is stationary or during translational and/or individual axial rotation of any biological unit.
• Figure 2 shows that the carousel 10 can rotate a total of ⁇ 180 degrees during translational movement (indicated by arrows) along the carousel frame where every biological production unit 16 can be moved to any position relative to a preferred access point for an operator. Movement can be either clockwise or counter clockwise. Movement is precisely controlled directionally in increments and with respect to a selected desired speed.
• the translational movement of the biological production units along the carousel track is optionally constrained to about ⁇ 180 degrees to preclude any tendency to compromise the integrity of the cabling (not shown) that supply resources (e.g. power, data, gases, etc.) from a central location within the vertical housing assembly and to each of the individual biological production units in succession.
• resources e.g. power, data, gases, etc.
• each biological production unit 16 can be independently and dynamically adjusted with respect to its axial orientation relative to gravity (arrows) in a bi-directional manner through a defined range of angles (also referred to as“tilting” or“rocking”). Dynamic axial rotational adjustment of any one of the biological production units can be effected during the unison translational movement of the biological production units along the carousel or when the carousel is stationary.
• Figure 4 shows the structure of the carousel 10 of the invention supporting one cantilevered biological production unit 16 for simplicity.
• the carousel 10 is orientated upright (vertical) and comprises a track assembly 18 having a drive track 20 and a support track 22 that are spaced apart, substantially parallel to one another, and mechanically affixed to a rigid support frame (not shown).
• the carousel 10 can also be oriented substantially vertically, such that drive track 20 and support track are angled related to perpendicular, for example at an about of about 0°-60° relative to completely vertical (perpendicular to the ground or floor).
• Each of the drive track 20 and the support track 22 is shown to be oval (a closed loop) in shape and orientated so that the long runs of the loop extend vertically and the track bends are located on the top and bottom of the tracks.
• the drive track is positioned forwardly to the support track as it is coupled with the biological production unit that requires user access.
• the support track is spaced vertically lower with respect to the drive track. This vertical off-set is fixed.
• a translation assembly 24 is shown that acts as the mechanical linkage connecting the drive track 20 and the support track 22 providing simultaneous translational movement along the connected tracks.
• the translation assembly is configured to couple with a biological production unit 16 at one end that is adjacent the drive track 20.
• the biological production unit 16 is shown to be individually mounted to the translation assembly 24 in a cantilevered position via a single cantilevered fixed reversible coupling (not shown).
• the translation assembly enables a cantilevered positioning of the biological production unit.
• the single attachment point for each cantilevered biological production unit enhances service access to each of the biological production units and further improves overall space efficiency.
• the cantilevered fixed reversible coupling allows for coupling and uncoupling such that any given biological production unit can be removed/detached from the arm assembly of the carousel and replaced or relocated to another position on the carousel. While one translation assembly is shown, is understood by one of skill in the art, that multiple translation assemblies are mounted in a desired spaced relationship linking the drive track to the support track each supporting a cantilevered biological production unit.
• the automated carousel must offer geometric stability by means of ensuring each production unit remains precisely aligned relative to the gravity vector throughout positional adjustment/rotation of the automated carousel.
• Systems where orientation is not critical employ the use of gravity as a mechanism for alignment, where the center of mass is lower than the pivot point of the object.
• Such systems inadequately compensate for changes in the center of mass, which influences the position of the gravity vector relative to the object undergoing movement.
• the automated carousel described herein specifically orients the biological production unit relative to the gravity vector such that secondary operations within the biological production unit that influence the center of mass do not affect orientation relative to gravity.
• the resulting stability of the biological production unit(s) enables the movement of internal components relative to the gravity vector to achieve specific biological or fluidic events.
• an additional linkage is implemented for independent control of the orientation of the production unit (as shown in Figure 3).
• FIG. 5 more closely shows the structure of the translation assembly 24 is configured for synchronous translational movement along the tracks while supporting the biological production unit 16 in a cantilevered orientation.
• the translation assembly 24 comprises a horizontal hub assembly 28 having a first end 30 with a cantilevered fixed reversible coupling (not shown) that extends laterally to receive a shaft of the biological production unit 16.
• the horizontal hub assembly 28 also comprises a central hub 32 with a rigid extension 33 to support a drive carriage 36 that cooperatively engages the drive track 20 and its associated drive means (e.g. drive belt or drive linkage, not shown).
• the horizontal hub assembly has a second end 38 to which, via inner hub, is fixedly mounted a vertically downward extending resistance arm 40.
• the resistance arm 40 extends in a downwards orientation parallel to both tracks to which a support carriage 42 is affixed at its lowest end via a pivot mounting.
• the support carriage 42 cooperatively engages the support track 22 and its associated drive means (e.g. drive belt or drive linkage, not shown).
• the drive carriage and the support carriage travel synchronously around the oval tracks such that the resistance arm 40 is always maintained in a vertical orientation by virtue of a geometrical constraint arising from the fixed vertical offset of the drive track 20 and support track 22.
• a translation assembly to support the biological production unit enables the repositioning of the biological production unit to a location that is convenient for operator access to the cell and/or tissue culture system supported therein. While only one biological production unit is shown, a plurality of translation assemblies may be configured to travel along the tracks with each supporting a cantilevered biological production unit. The relative position of each translation assembly may be constrained by interconnecting linkages. Furthermore, it is feasible to provide adjustable spacing for the positions of the biological production units whereby spacing is exaggerated for locations where unconstrained operator access is required and reduced in locations where no operator access is required, such as the rear aspect of the carousel.
• the provision of the two mechanically and operationally linked carriages also provides the mechanical rigidity that is required to resist any bending moment imparted on the drive rack by the cantilevered biological production unit. It is understood by one of skill in the art that the distance between the drive track and the support track may vary and this in part may be due to the size of the translation assembly providing linkage between the two tracks, the size and weight of the biological production units and the engineering forces required for adequate cantilevered mounting of multiple units. While the biological production units are shown cantilevered using a cantilevered mount, it is understood that other mounts with other orientations may be used. Furthermore, where only one biological production unit is shown to be cantilevered at each translation assembly, it is understood that smaller biological units may be used and thus more than one biological unit may be mounted in a cantilevered position, either in series or adjacent to each translation assembly.
• the shape and size of the drive track and the support track should be substantively the same for proper translational movement along the carousel tracks and orientation with respect to gravity. While the tracks of the frame are shown to be substantially oval in shape, the shape can vary and is limited only by the ability to space apart the biological production units that are supported on the carousel and the ability to provide about ⁇ 180 degrees of rotational bidirectional movement. Therefore, the tracks can be substantially oval, substantially elliptical, substantially circular or substantially capsule-shaped.
• the carousel can be designed to be of any vertical height (e.g. size) limited by only the facility in which it will be used.
• the two tracks that make up the frame of the carousel can be may of any desired thickness and made of suitable materials that can withstand stress cycles and dynamic loading conditions during its use.
• suitable materials comprise typically used engineering materials such as but not limited to metals and metal alloys (e.g. comprising high grade stainless steel, steel alloys, iron, copper, aluminum and combinations thereof).
• Figure 6 shows the translation assembly 24 in isolation with a portion of the central hub 32 cut away.
• the translation assembly 24 shows a central section that is a horizontal hub assembly 28.
• the first end 30 of the horizontal hub assembly has a cantilevered fixed reversible coupling 26 to mount a biological production unit.
• the central hub 32 has an outer hub shell 34 having one side affixed, via rigid extension, to a drive carriage 36 that cooperatively engages with the drive track for translational movement thereon.
• An inner hub 44 is retained via bearings within the outer hub shell 34.
• the inner hub 44 is constrained from rotating within the outer hub shell by way of the resistance arm 40 fixedly mounted to the inner hub and projecting vertically downward to connect with a support carriage 42 via a pivot connection and configured to cooperatively engage the support track 22 and its associated driven means (not shown).
• the outer hub shell 34 undergoes rotational inversion while traveling the oval path of the primary track, the inner hub is constrained to maintain a consistent orientation relative to gravity by virtue of the attached resistance arm being constrained to remain vertical.
• This constraint on the orientation of the resistance arm occurs due to the cooperative positioning of the drive carriages and support carriages wherein the drive carriage is always positioned vertically above the secondary carriage when the carriages are traveling around the tracks.
• the coupling 26 supporting the cantilevered biological production unit mechanically engages with a motor driven central shaft 54 within the inner hub 44 of the via bearings.
• the motor driven central shaft is either constrained from rotating within the inner hub 44 or actively rotated at a controlled speed by the motor drive and gearbox mounted on the inner hub that drives the axial rotational of the central shaft.
• the drive carriage 36 is a drive block assembly 56 with one face thereof 58 having affixed vertically arranged pairs of outwardly projecting bearing members 60 for gripping the primary track 20 and engaging its associated drive means adapted translational movement along the course of travel defined by the primary track.
• the support carriage 42 is a support block assembly 62 with one face thereof 64 having affixed vertically arranged pairs of outwardly projecting bearing members 66 for gripping the support track for moving along the course of travel defined by the support track.
• the support carriage actively translationally moves along the support track in a synchronous manner with the drive carriage while retaining the fixed vertical offset according to the length of the lever arm.
• the translation assembly 24 and similar translation assemblies present on the tracks are moved in unison through physical connection of the primary carriage to a primary drive belt and motor assembly and a secondary drive belt linking the secondary carriages.
• the motion is a gliding motion with minimal friction based on the bearing interface between the carriages and the tracks.
• the carriages support significant lateral and bending loads. This load carrying capability and the use of two carriages offset via the translation assembly enables significant cantilever loads to be resisted thereby ensuring stable translation of the biological product units from position to position.
• the biological production unit 16 is rigidly mounted to the translation assembly 24 via the cantilevered fixed reversible coupling 26 that cooperates with the motor driven central shaft 54 retained within the inner central hub 44.
• the inner central hub always maintains a consistent orientation relative to the gravity vector.
• the motor drive assembly positions the axial rotation of the central shaft 54 relative to the inner central hub.
• the biological production unit (thus the cell and/or tissue culture system contained therein) will maintain a given orientation relative to the gravity vector.
• the axial position of central shaft 54 may be changed in either direction, thereby dynamically axially changing the position of the cell and/or tissue culture system relative to the gravity vector.
• This changing of the axial orientation of the biological production unit may be intermittent to aid a specific biological activity occurring within a cassette mounted within a biological production unit or may be continuous (e.g. rocking or tilting) of a bioreactor within the cassette housed in the biological production unit.
• Figure 7 shows a fully populated carousel illustrating the positioning of the translation assembly components with respect to the different positions of the biological production unit on the carousel both in the long runs and on the track bends. It is clear that regardless of the position of the biological production units along the tracks the resistance arm 40 is retained in its vertical position. During translational movement along the track bends, the outer hub shell 34 and the drive carriage 36 undergo rotational inversion while at the same time the support carriage pivots to undergo inversion. The drive carriages and the associated support carriages
• each biological production unit is independently controlled with respect to the biological processing conditions occurring therein. This necessitates the delivery of common resources to each biological production unit, where the consumption of such resources is controlled internally within each production unit.
• the rotational movement of the plurality of biological production units presents a unique challenge for resource delivery and management.
• a limit of about ⁇ 180 degrees rotation for the automated carousel is suitable.
• auxiliaries and resources e.g. electrical power, supply gases and data.
• FIG 8 shows the complexity of a representative fully populated carousel operationally supported on the vertical housing assembly 12 supporting central operational resources for delivery.
• each biological production unit is functionally attached via cabling (70) inserted via the port connection 50 that extends and is connected to the centrally located source within the vertical housing assembly 12.
• Cabling 70 from the central source is connected to a first biological production unit and onward to each successive biological production unit.
• This interlinked cabling strategy precludes the complexity of establishing independent cabling for resources for every biological production unit to the centrally located source.
• Safety precautions are an operational requirement for the automated carousel in order to protect both the operator and the ongoing viability of the biological processes underway within each biological production unit.
• Moving parts are either contained or have an uninterrupted surface relative to other moving/stationary parts to prevent pinch points. In the event these conditions are not possible, alternate methods for avoiding injury are required.
• the housing assembly shown in Figure 8 is configured with a protective cover 72 to further help to isolate and thus protect users from the resource distribution network and other parts.
• a safety clutch is also provided to allow automatic interruption of movement of the carousel in the event higher than normal torque is encountered by the drive system of the automated carousel.
• the clutch slip at high torques protects the user from pinch hazards that can be created by the biological production units rotating along the track orbit and also avoids potentially damaging torques being transferred to other components within the automated carousel in the event of a malfunction.
• Service and cleaning of the automated carousel is required for operation within GMP facilities.
• the temporary relocation of the automated carousel is potentially advantageous in maintaining a clean production space.
• Wheels 74 present underneath the base 14 are configured to deploy when portability is required. When stationary, the wheels 74 are retracted within the base to ensure stable placement of the base 14 relative to the underlying floor structure.
• Figure 10 shows representative configurations/sizes of the carousel supporting from 6 to 10 biological production units thereon. Fully populated“housed” carousels are also shown in series illustrating the much increased production capabilities of a biological facility for cell and/or tissue culture engineering.
• a carousel can be configured/ sized to accommodate any number of biological production units.
• the height of the carousel is typically determined by the overhead clearance in the building in which it is to be installed.
• the carousel is constructed to have a maximum height compatible with the building structure to maximize the number of biological production units supported on a given carousel.
• a carousel can be two or more stories in height, fitting within a two-three story (or more) building, to maximize the use of vertical space in the biological facility.
• scaffolding and/or platforms can be added to the carousel to add structural integrity as well as to provide additional working areas for scientists to stand and monitor the biological production.
• the carousel can also span or physically incorporate walkways or platforms that allow technicians to access the carousel at different heights, and also allow for multiple access points to multiple users. Additional laboratory equipment can also be housed on the platforms as desired or needed to provide multiple working areas.
• a carousel can also be used to allow the movement of biological production units from one environmental class to another.
• the carousel can span a sufficient height that a bottom section has a first cleanroom classification (e.g., a regulated cleanroom environment), then allow for translation of the biological production unit to an upper section that has a different clean room classification (e.g., an unregulated cleanroom environment, to allow for different production unit interactions to occur under different environmental conditions).
• a first cleanroom classification e.g., a regulated cleanroom environment
• a different clean room classification e.g., an unregulated cleanroom environment, to allow for different production unit interactions to occur under different environmental conditions.
• Additional classifications can be envisioned as well.
• the spacing between the biological production units is adjustable and is selected to provide adequate spacing for the size of the biological production unit. This allows
• the carousel and carousel systems may further be configured to have the separate ability to adjust the spacing of each biological unit relative to adjacent biological units so as to maximize the spatial density of biological units in selected zones of the carousel by close spacing and enhance user access to biological units in other selected zones by open spacing.
• adjacent biological production units may be further translationally repositioned“away” from the selected biological production unit to provide more room for a user.
• the biological production units may be precisely positioned for a selected user, by the user.
• An interface for the user to communicate effectively to each biological production unit on the carousel is provided and is adjustable.
• Figure 11 demonstrates representative measurements that can be used to define the range of placement of any specific production unit in order to provide ergonomic access by an operator.
• using the automated carousel of the invention not only increases biological production, but provides a user easy and comfortable access to any one of the biological units either for inspection, for replacement, for removal or for repositioning.
• a user may place any of the biological production units at a vertical ergonomic level while standing or sitting.
• the biological production units 16 are configured to move in unison or separately, so as to enable vertical positioning of any single unit for easy access.
• one or more additional stationary units can be mounted to the carousel as workflow units. These workflow units can be utilized for specific functions by removing a cassette from a unit currently translating in the carousel series, and transferring it to the stationary unit for additional processing.
• the stationary workflow units can also be utilized as a resource in the event temporary operational support is required to address a single biological production unit malfunction event. This temporary role can support unit repair or unit replacement.
• a secondary processing module can also be included in the carousels described herein.
• This secondary processing module can be engaged when a biological production unit 16 reaches a specific position in the translation.
• the secondary processing module can be a bio-isolator to generate a controlled environment around a particular production unit for specific cassette handling requirements or other technical functions. This bio isolator could allow an operator to intervene in the operation of a unit in ways not possible should the unit open into the general space (e.g., either external contamination, or a highly specialized or potentially toxic cell or virus being used in the units).

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